Thyroid hormone (T3) is critical for vertebrate development and affects the function of many adult tissues and organs. Its genomic effects are mediated by thyroid hormone nuclear receptors (TRs) present in all vertebrates. Recent discovery of human patients carrying heterozygous mutations in the THRA gene (RTHalpha) revealed a distinct phenotype that was not observed in the RTH patients with THRB gene mutations (RTHbeta). That is, the RTHalpha patients have constipation, implicating intestinal defects caused by THRA gene mutations. To determine how TRalpha1 mutations affect the intestine, we have analyzed the histology of intestine in TRalpha1PV mice. We found that adult TRalpha1PV/+ mice exhibit constipation just like in patients with TRalpha mutations. Importantly, we discovered significant intestinal defects, including shorter villi, increased differentiated cells in the crypt, accompanied by reduced stem cell proliferation in the intestine. Our findings suggest that further analysis of this mouse model should help reveal the molecular and physiological defects in the intestine caused by TRalpha mutations.